ABSTRACT
Since biological membranes are composed of lipids and proteins we tested the in vitro antioxidant properties of several indoleamines from the tryptophan metabolic pathway in the pineal gland against oxidative damage to lipids and proteins of synaptosomes isolated from the rat brain. Free radicals were generated by incubation with 0.1 mM FeCl(3), and 0.1 mM ascorbic acid. Levels of malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA), and carbonyl content in the proteins were measured as indices of oxidative damage to lipids and proteins, respectively. Pinoline was the most powerful antioxidant evaluated, with melatonin, N-acetylserotonin, 5-hydroxytryptophan, 5-methoxytryptamine, 5-methoxytryptophol, and tryptoline also acting as antioxidants.
Subject(s)
Free Radicals/toxicity , Intracellular Membranes/drug effects , Melatonin/pharmacology , Neuroprotective Agents/pharmacology , Synaptosomes/drug effects , 5-Hydroxytryptophan/metabolism , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Carbolines/metabolism , Intracellular Membranes/metabolism , Kinetics , Male , Melatonin/analogs & derivatives , Melatonin/chemistry , Neuroprotective Agents/chemistry , Oxidation-Reduction/drug effects , Rats , Synaptosomes/metabolism , Tryptophan/metabolismABSTRACT
Prolonged exposure to excessive aluminium (Al) concentrations is involved in the ethiopathology of certain dementias and neurological disorders. Melatonin is a well-known antioxidant that efficiently reduces lipid peroxidation due to oxidative stress. Herein, we investigated in synaptosomal membranes the effect of melatonin in preventing Al promotion of lipid and protein oxidation when the metal was combined with FeCl(3) and ascorbic acid. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations in the membrane suspension and protein carbonyls were measured in the synaptosomes as an index of oxidative damage. Under our experimental conditions, the addition of Al (0.0001-1mmol/L) enhanced MDA+4-HDA formation in the synaptosomes. In addition, Al (1mmol/L) raised protein carbonyl contents. Melatonin reduced, in a concentration-dependent manner, lipid and protein oxidation due to Al, FeCl(3) and ascorbic acid in the synaptosomal membranes. These results show that melatonin confers protection against Al-induced oxidative damage in synaptosomes and suggest that this indoleamine may be considered as a neuroprotective agent in Al toxicity because of its antioxidant activity.
Subject(s)
Aluminum/metabolism , Lipids/chemistry , Melatonin/metabolism , Oxidative Stress , Proteins/metabolism , Synaptosomes/metabolism , Animals , Antioxidants/metabolism , Lipid Peroxidation , Neuroprotective Agents/metabolism , Oxidation-Reduction , Rats , Rats, Sprague-Dawley , Synaptosomes/chemistry , Synaptosomes/pathologyABSTRACT
Numerous data indicate that hyperhomocysteinemia is a risk factor for cardio- and cerebrovascular diseases. At least in part, homocysteine (HCY) impairs cerebrovascular function because it generates large numbers of free radicals. Since melatonin is a well-known antioxidant, which reduces oxidative stress and decreases HCY concentrations in plasma, the aim of this study was to investigate the effect of melatonin in preventing HCY-induced protein and lipid oxidation in rat brain homogenates. Brain homogenates were obtained from Sprague-Dawley rats and were incubated with or without HCY (0.01-5 mM) or melatonin (0.01-3 mM). Carbonyl content of proteins, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations in the brain homogenates were used as an index of protein and lipid oxidation, respectively. Under the experimental conditions used, the addition of HCY (0.01-5 mM) to the homogenates enhanced carbonyl protein and MDA+4-HDA formation. Melatonin reduced, in a concentration-dependent manner, protein and lipid oxidation due to HCY in the brain homogenates. These data suggest that preserving proteins from oxidative insults is an additional mechanism by which melatonin may act as an agent in potentially decreasing cardiovascular and cerebrovascular diseases related to hyperhomocysteinemia.
Subject(s)
Brain/metabolism , Homocysteine/chemistry , Melatonin/chemistry , Alkenes/chemistry , Animals , Antioxidants/chemistry , Antioxidants/metabolism , Dose-Response Relationship, Drug , Humans , Lipid Peroxidation , Models, Biological , Oxidants/metabolism , Oxidative Stress , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
No disponible
Subject(s)
Humans , Aging/physiology , Oxidative Stress/physiology , Free Radicals/analysisABSTRACT
The serum concentrations of aluminum, a metal potentially involved in the pathogenesis of Alzheimer's disease, increase with age. Also, intense and prolonged exposure to aluminum may result in dementia. Melatonin and pinoline are two well known antioxidants that efficiently reduce lipid peroxidation due to oxidative stress. Herein, we investigated the effects of melatonin and pinoline in preventing aluminum promotion of lipid peroxidation when the metal was combined with FeCl3 and ascorbic acid in rat synaptosomal membranes. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations in the membrane suspension. Under the experimental conditions used herein, the addition of aluminum (0.0001 to 1 mmol/L) enhanced MDA + 4-HDA formation in the synaptosomes. Melatonin and pinoline reduced, in a concentration-dependent manner, lipid peroxidation due to aluminum, FeCl3 and ascorbic acid in the synaptosomal membranes. These results suggest that the indoleamine melatonin and the beta-carboline pinoline may potentially act as neuroprotectant agents in the therapy of those diseases with elevated aluminum concentrations in the tissues.
